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Publication numberUS20030181958 A1
Publication typeApplication
Application numberUS 10/243,612
Publication date25 Sep 2003
Filing date13 Sep 2002
Priority date22 Mar 2002
Also published asUS7239912, US7937144, US8024035, US8340760, US20070219596, US20070225768, US20110178568, US20110319969
Publication number10243612, 243612, US 2003/0181958 A1, US 2003/181958 A1, US 20030181958 A1, US 20030181958A1, US 2003181958 A1, US 2003181958A1, US-A1-20030181958, US-A1-2003181958, US2003/0181958A1, US2003/181958A1, US20030181958 A1, US20030181958A1, US2003181958 A1, US2003181958A1
InventorsJohn Dobak
Original AssigneeDobak John D.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Electric modulation of sympathetic nervous system
US 20030181958 A1
Abstract
A method for the treatment of obesity or other disorders, by electrical activation or inhibition of the sympathetic nervous system. This activation or inhibition can be accomplished by electrically stimulating the greater splanchnic nerve or other portion of the sympathetic nervous system using an implantable pulse generator. This nerve activation can result in reduced food intake and increased energy expenditure. Reduced food intake may occur through a variety of mechanisms that reduce appetite and cause satiety. Increased adrenal gland hormone levels will result in increased energy expenditure. Fat and carbohydrate metabolism, which are also increased by sympathetic nerve activation, will accompany the increased energy expenditure.
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Claims(48)
I claim:
1. A method for treating a medical condition by electrically modulating the sympathetic nervous system.
2. The method recited in claim 1, wherein said modulation comprises activation of the sympathetic nervous system.
3. The method recited in claim 2, wherein said activation comprises activation of the splanchnic nerve to induce weight loss.
4. The method recited in claim 3, wherein said activation of the splanchnic nerve induces weight loss by reducing appetite.
5. The method recited in claim 4, wherein said activation of the splanchnic nerve reduces appetite by reducing plasma ghrelin hormone levels.
6. The method recited in claim 3, wherein said activation of the splanchnic nerve induces weight loss by increasing energy expenditure.
7. The method recited in claim 6, wherein said activation of the splanchnic nerve increases energy expenditure by increasing plasma catecholamine levels.
8. The method recited in claim 3, wherein said activation of the splanchnic nerve induces weight loss by normalizing catecholamine levels.
9. The method recited in claim 3, wherein said activation of the splanchnic nerve induces weight loss by inducing satiety.
10. The method recited in claim 9, wherein said activation reduces gastric motility.
11. The method recited in claim 9, wherein said activation increases pyloric sphincter tone.
12. The method recited in claim 9, wherein said activation delays gastric emptying.
13. The method recited in claim 2, wherein said activation comprises activation of the sympathetic chain ganglia.
14. The method recited in claim 13, wherein said activation of sympathetic chain ganglia comprises activation of ganglia in the thoracic region from T4 to T12.
15. The method recited in claim 2, wherein said activation comprises activation of peripheral sympathetic ganglia.
16. The method recited in claim 15, wherein said activation of peripheral ganglia comprises activation of at least one ganglia selected from the group of the celiac ganglia, the superior mesenteric ganglia, and the inferior mesenteric ganglia.
17. The method recited in claim 2, wherein said activation comprises:
activation of the splanchnic nerve to reduce plasma ghrelin levels, thereby reducing appetite;
activation of the splanchnic nerve to increase plasma glucose levels, thereby reducing appetite; and
activation of the splanchnic nerve to increase plasma catecholamine levels, thereby increasing energy expenditure.
18. The method recited in claim 2, wherein said activation comprises activation of the splanchnic nerve to reduce insulin secretion.
19. The method recited in claim 2, wherein said activation of the sympathetic nervous system treats Type II diabetes.
20. The method recited in claim 2, wherein said activation comprises activation of the splanchnic nerve to treat irritable bowel syndrome.
21. The method recited in claim 1, wherein said modulation comprises inhibition of the sympathetic nervous system.
22. The method recited in claim 21, wherein said inhibition comprises inhibition of the splanchnic nerve to relieve pain.
23. The method recited in claim 21, wherein said inhibition comprises inhibition of the splanchnic nerve to treat anorexia.
24. The method recited in claim 1, wherein said modulation comprises modulation of the celiac ganglia.
25. The method recited in claim 1, wherein said modulation comprises modulation of the sympathetic chain ganglia.
26. A method for treating obesity, comprising:
monitoring a selected patient parameter; and
electrically activating the sympathetic nervous system of said patient to achieve a desired level in said monitored parameter.
27. The method recited in claim 26, wherein:
said monitored parameter is plasma catecholamine level; and
said electrical activation comprises activation of the sympathetic nervous system to achieve an increased plasma catecholamine level, thereby increasing energy expenditure.
28. The method recited in claim 26, wherein:
said monitored parameter is plasma catecholamine level; and
said electrical activation comprises activation of the sympathetic nervous system to achieve normalization of reduced catecholamine levels.
29. The method recited in claim 26, wherein:
said monitored parameter is plasma ghrelin level; and
said electrical activation comprises activation of the sympathetic nervous system to achieve a decreased plasma ghrelin level, thereby decreasing appetite.
30. The method recited in claim 26, wherein:
said monitored parameter is mean arterial blood pressure; and
said electrical activation comprises activation of the sympathetic nervous system with stimulation parameters that prevent a rise in mean arterial blood pressure.
31. The method recited in claim 26, wherein said monitored parameter is mean arterial blood pressure, said method further comprising simultaneously delivering an alpha-adrenergic receptor blocking drug to said patient.
32. A method for treating a medical condition, comprising:
electrically activating the sympathetic nervous system; and
simultaneously administering an alpha-adrenergic receptor blocking drug.
33. A method for treating a medical disorder, comprising:
monitoring a patient vital sign and a second selected patient parameter; and
electrically activating the sympathetic nervous system of said patient to achieve a desired change in said second selected patient parameter while limiting change in said vital sign.
34. The method recited in claim 33, wherein:
said medical disorder being treated is obesity;
said vital sign is mean arterial blood pressure;
said monitored parameter is plasma catecholamine level;
said electrical activation comprises activation of the sympathetic nervous system to achieve an increased plasma catecholamine level, thereby increasing at-rest energy expenditure; and
said electrical activation has a signal-on time no greater than the signal-off time, thereby preventing an increase in mean arterial blood pressure.
35. The method recited in claim 33, wherein:
said medical disorder being treated is obesity;
said vital sign is mean arterial blood pressure;
said monitored parameter is plasma ghrelin level;
said electrical activation comprises activation of the sympathetic nervous system to achieve a decreased plasma ghrelin level, thereby decreasing appetite; and
said electrical activation has a signal-on time no greater than the signal-off time, thereby preventing an increase in mean arterial blood pressure.
36. The method recited in claim 33, wherein:
said medical disorder being treated is obesity;
said vital sign is mean arterial blood pressure;
said monitored parameter is plasma glucose level;
said electrical activation comprises activation of the sympathetic nervous system to achieve an increased plasma glucose level, thereby decreasing appetite; and
said electrical activation has a signal-on time no greater than the signal-off time, thereby preventing an increase in mean arterial blood pressure.
37. The method recited in claim 33, wherein:
said medical disorder being treated is Type II diabetes;
said vital sign is mean arterial blood pressure;
said monitored parameter is insulin level;
said electrical activation comprises activation of the sympathetic nervous system to achieve a decreased insulin level, thereby reducing insulin resistance; and
said electrical activation has a signal-on time no greater than the signal-off time, thereby preventing an increase in mean arterial blood pressure.
38. A procedure for implanting an electrode on the splanchnic nerve, comprising:
providing an introducer needle insulated except at its tip;
inserting said introducer needle into a patient;
applying an electrical pulse to said introducer needle;
varying the current amplitude of said electrical pulse;
monitoring for at least one change in at least one vital sign indicative of proximity of said introducer needle to the splanchnic nerve, said at least one vital sign change being selected from the group of a rise in mean arterial pressure and a decrease in heart rate; and
inserting an electrode and lead assembly through said introducer needle to place said electrode adjacent to the splanchnic nerve.
39. A method for activating the splanchnic nerve to treat obesity, said method comprising:
applying a current pulse to the splanchnic nerve; and
selecting the duration of said current pulse to be no greater than the chronaxie of the splanchnic nerve.
40. The method recited in claim 39, further comprising selecting said duration of said pulse to be between 100 microseconds and 400 microseconds.
41. A method for activating the splanchnic nerve to treat obesity, said method comprising:
implanting a pulse generator within a patient, said pulse generator having programmable signal-on and signal-off times;
applying a current pulse to the splanchnic nerve with said pulse generator; and
programming said signal-on and signal-off times to maintain plasma epinephrine levels between 50 pg/ml and 1000 pg/ml.
42. A method for activating the splanchnic nerve to treat obesity, said method comprising:
implanting a pulse generator within a patient, said pulse generator having programmable treatment parameters;
applying a current pulse to the splanchnic nerve with said pulse generator; and
programming said treatment parameters to maintain plasma ghrelin levels below 250 pg/ml.
43. A method for treating a medical condition, comprising:
providing a pulse generator having programmable stimulation parameters;
programming said parameters to stimulate type B neurons; and
activating the sympathetic nervous system with said pulse generator.
44. The method recited in claim 43, wherein said stimulation parameters comprise current amplitude and pulse width, said method further comprising programming said pulse generator to produce a pulse having a current amplitude and a pulse width adapted to activate type B neurons.
45. A method for treating obesity, comprising unipolar stimulation of the splanchnic nerve.
46. The method recited in claim 45, further comprising:
placing a first electrode in general proximity to the splanchnic nerve; and
generating a sufficiently large energy field with said first electrode to electrically couple with a second electrode remote from said first electrode, said energy field being sufficiently large to stimulate a splanchnic nerve in general proximity to said first electrode.
47. The method recited in claim 46, further comprising:
implanting a pulse generator within a patient, remote from said splanchnic nerve, said pulse generator having an external portion adapted to function as said remote second electrode; and
applying a current pulse to said first electrode with said pulse generator, said current pulse being sufficiently large to electrically couple said first electrode with said external portion of said pulse generator.
48. The method recited in claim 47, further comprising providing a housing on said pulse generator adapted to function as said second electrode.
Description
    CROSS REFERENCE TO RELATED APPLICATIONS
  • [0001]
    This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/366,750, filed on Mar. 22, 2002, and entitled “Sympathetic Nervous System Electrical Stimulation for Weight Control”; U.S. Provisional Patent Application Serial No. 60/370,311, filed on Apr. 5, 2002, and entitled “Splanchnic Nerve Stimulation and Anchoring to the Crus of the Diaphragm for Obesity Treatment”; U.S. Provisional Patent Application Serial No. 60/379,605, filed on May 10, 2002, and entitled “Percutaneous Placement of an Electrode for Splanchnic Nerve Stimulation with and without Thorascopic Visualization for Obesity and Diabetes Therapy”; U.S. Provisional Patent Application Serial No. 60/384,219, filed on May 30, 2002, and entitled “Sympathetic Nervous System Electrical Stimulation for Weight Control”; and U.S. Provisional Patent Application Serial No. 60/386,699, filed on Jun. 10, 2002, and entitled “Treatment of Obesity and Other Medical Conditions Through Electrical Nerve Modulation of the Sympathetic Nervous System”.
  • STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
  • [0002]
    Not Applicable
  • BACKGROUND OF THE INVENTION
  • [0003]
    1. Field of the Invention
  • [0004]
    This invention is in the field of nerve stimulation for the treatment of medical conditions.
  • [0005]
    2. Background Art
  • [0006]
    Obesity is considered an epidemic in the U.S. with a prevalence of 19.8%. The annual healthcare costs associated with obesity are estimated to exceed $200 BB. Obesity is defined as a body mass index (BMI) that exceeds 30 kg/m2. Normal BMI is 18.5-25 kg/m2 and overweight persons have BMIs of 25-30. Obesity is classified into three groups moderate (Class 1), severe (Class II), and very severe (Class III). Patients with BMIs that exceed 30 are at risk for significant comorbidities such as diabetes, heart and kidney disease, dyslipidemia, hypertension, sleep apnea, and orthopedic problems.
  • [0007]
    Obesity results from an imbalance between food intake and energy expenditure such that there is a net increase in fat reserves. Excessive food intake, reduced energy expenditure, or both may cause this imbalance. Appetite and satiety, which control food intake, are partly controlled in the brain by the hypothalamus. Energy expenditure is also partly controlled by the hypothalamus. The hypothalamus regulates the autonomic nervous system of which there are two branches, the sympathetic and the parasympathetic. The sympathetic nervous system generally prepares the body for action by increasing heart rate, blood pressure, and metabolism. The parasympathetic system prepares the body for rest by lowering heart rate, lowering blood pressure, and stimulating digestion. Destruction of the lateral hypothalamus results in hunger suppression, reduced food intake, weight loss, and increased sympathetic activity. In contrast, destruction of the ventromedial nucleus of the hypothalamus results in suppression of satiety, excessive food intake, weight gain, and decreased sympathetic activity. The splanchnic nerves carry sympathetic neurons that supply, or innervate, the organs of digestion and adrenal glands, and the vagus nerve carries parasympathetic neurons that innervate the digestive system and are involved in the feeding and weight gain response to hypothalamic destruction.
  • [0008]
    Experimental and observational evidence suggests that there is a reciprocal relationship between food intake and sympathetic nervous system activity. Increased sympathetic activity reduces food intake and reduced sympathetic activity increases food intake. Certain peptides (e.g. neuropeptide Y, galanin) are known to increase food intake while decreasing sympathetic activity. Others such as cholecystokinin, leptin, enterostatin, reduce food intake and increase sympathetic activity. In addition, drugs such as nicotine, ephedrine, caffeine, subitramine, dexfenfluramine, increase sympathetic activity and reduce food intake.
  • [0009]
    Ghrelin is another peptide that is secreted by the stomach that is associated with hunger. Peak plasma levels occur just prior to meal time, and ghrelin levels are increased after weight loss. Sympathetic activity may suppress ghrelin secretion.
  • [0010]
    Appetite is stimulated by various psychosocial factors, but is also stimulated by low blood glucose levels. Cells in the hypothalamus that are sensitive to glucose levels are thought to play a role in hunger stimulation. Sympathetic activity increases plasma glucose levels. Satiety is promoted by distension of the stomach and delayed gastric emptying. Sympathetic activity reduces duodenal motility and increases pyloric sphincter, which may result in distention and delayed gastric emptying.
  • [0011]
    The sympathetic nervous system plays a role in energy expenditure and obesity. Genetically inherited obesity in rodents is characterized by decreased sympathetic activity to adipose tissue and other peripheral organs. Catecholamines and cortisol, which are released by the sympathetic nervous system, cause a dose-dependent increase in resting energy expenditure. In humans, there is a reported negative correlation between body fat and plasma catecholamine levels. Overfeeding or underfeeding lean human subjects has a significant effect on energy expenditure and sympathetic nervous system activation. For example, weight loss in obese subjects is associated with a compensatory decrease in energy expenditure, which promotes the regain of previously lost weight. Drugs that activate the sympathetic nervous system, such as ephedrine, caffeine and nicotine, are known to increase energy expenditure. Smokers are known to have lower body fat stores and increased energy expenditure.
  • [0012]
    The sympathetic nervous system also plays an important role in regulating energy substrates for increased expenditure, such as fat and carbohydrate. Glycogen and fat metabolism are increased by sympathetic activation and are needed to support increased energy expenditure.
  • [0013]
    Animal research involving acute electrical activation of the splanchnic nerves under general anesthesia causes a variety of physiologic changes. Electrical activation of a single splanchnic nerve in dogs and cows causes a frequency dependent increase in catecholamine, dopamine, and cortisol secretion. Plasma levels can be achieved that cause increased energy expenditure. In adrenalectomized anesthetized pigs, cows, and dogs, acute single splanchnic nerve activation causes increased blood glucose and reduction in glycogen liver stores. In dogs, single splanchnic nerve electrical activation causes increased pyloric sphincter tone and decrease duodenal motility. Sympathetic and splanchnic nerve activation can cause suppression of insulin and leptin hormone secretion.
  • [0014]
    First line therapy for obesity is behavior modification involving reduced food intake and increased exercise. However, these measures often fail and behavioral treatment is supplemented with pharmacologic treatment using the pharmacologic agents noted above to reduce appetite and increase energy expenditure. Other pharmacologic agents that may cause these affects include dopamine and dopamine analogs, acetylcholine and cholinesterase inhibitors. Pharmacologic therapy is typically delivered orally and results in systemic side effects such as tachycardia, sweating, and hypertension. In addition, tolerance can develop such that the response to the drug reduces even at higher doses.
  • [0015]
    More radical forms of therapy involve surgery. In general, these procedures reduce the size of the stomach and/or reroute the intestinal system to avoid the stomach. Representative procedures are gastric bypass surgery and gastric banding. These procedures can be very effective in treating obesity, but they are highly invasive, require significant lifestyle changes, and can have severe complications.
  • [0016]
    Experimental forms of treatment for obesity involve electrical stimulation of the stomach (gastric pacing) and the vagus nerve (parasympathetic system). These therapies use a pulse generator to electrically stimulate the stomach or vagus nerve via implanted electrodes. The intent of these therapies is to reduce food intake through the promotion of satiety and or reduction of appetite, and neither of these therapies is believed to affect energy expenditure. U.S. Pat. No. 5,423,872 to Cigaina describes a method for treating eating disorders by electrically pacing the stomach. The believed mechanism of action is the promotion of satiety by reducing gastric activity and consequently delaying stomach content emptying. Reduction of appetite may also occur, but this is unclear. U.S. Pat. No. 5,263,480 to Wemicke discloses a method for treating obesity by electrically activating the vagus nerve. This therapy may promote satiety as afferent fibers that are stimulated by stomach distention are carried in the vagus nerve. Neither of these therapies increases energy expenditure.
  • BRIEF SUMMARY OF THE INVENTION
  • [0017]
    The present invention includes a method for treating obesity or other disorders by electrically activating the sympathetic nervous system. Obesity can be treated by activating the efferent sympathetic nervous system, thereby increasing energy expenditure and reducing food intake. Stimulation is accomplished using a pulse generator and electrodes implanted near, or attached to, various areas of the sympathetic nervous system, such as the sympathetic chain ganglia, the splanchnic nerves (greater, lesser, least), or the peripheral ganglia (eg. celiac, mesenteric). Ideally, the obesity therapy will employ electrical activation of the sympathetic nervous system that innervates the digestive system, adrenals, and abdominal adipose tissue, such as the splanchnic nerves or celiac ganglia.
  • [0018]
    This method of obesity treatment may reduce food intake by a variety of mechanisms, including general increased sympathetic system activation and increasing plasma glucose levels upon activation. Satiety may be produced through direct affects on the pylorus and duodenum that cause stomach distension and delayed stomach emptying. In addition, food intake may be reduced by reducing ghrelin secretion.
  • [0019]
    This method of obesity treatment may also increase energy expenditure by causing catecholamine, cortisol, and dopamine release from the adrenal glands. The therapy could be titrated to the release of these hormones. Fat and carbohydrate metabolism, which are also increased by sympathetic nerve activation, will accompany the increased energy expenditure. Other hormonal effects induced by this therapy may include reduced insulin secretion. Alternatively, this method may be used to normalize catecholamine levels, which are reduced with weight gain.
  • [0020]
    Electrical sympathetic activation for treating obesity is ideally accomplished without causing a rise in mean arterial blood pressure (MAP). This may be achieved by using an appropriate stimulation pattern with a relatively short signal-on time followed by an equal or longer signal-off time. During activation therapy, a sinusoidal-like fluctuation in the MAP may occur with an average MAP that is within safe limits. Alternatively, an alpha sympathetic receptor blocker, such as prazosin, could be used to blunt the increase in MAP.
  • [0021]
    Electrical sympathetic activation may be titrated to the plasma level of catecholamines achieved during therapy. This would allow the therapy to be monitored and safe levels of increased energy expenditure to be achieved. The therapy could also be titrated to plasma ghrelin levels.
  • [0022]
    Electrical modulation (inhibition or activation) of the sympathetic nerves can also be used to treat other eating disorders such as anorexia or bulimia. For example, inhibition of the sympathetic nerves may be useful in treating anorexia. Electrical modulation of the sympathetic nerves may also be used to treat gastrointestinal diseases such as peptic ulcers, esophageal reflux, gastroparesis, and irritable bowel. For example, stimulation of the splanchnic nerves that innervate the large intestine may reduce the symptoms of irritable bowel syndrome, characterized by diarrhea. Pain may also be treated by electric nerve modulation of the sympathetic nervous system, as certain pain neurons are carried in the sympathetic nerves. This therapy may also be used to treat type II diabetes. These conditions may require varying degrees of inhibition or stimulation.
  • [0023]
    The novel features of this invention, as well as the invention itself, will be best understood from the attached drawings, taken along with the following description, in which similar reference characters refer to similar parts, and in which:
  • BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
  • [0024]
    [0024]FIG. 1 is a diagram of the efferent autonomic nervous system;
  • [0025]
    [0025]FIG. 2 is a diagram of sympathetic nervous system anatomy;
  • [0026]
    [0026]FIG. 3 is an elevation view of the splanchnic nerves and celiac ganglia;
  • [0027]
    [0027]FIG. 4 is a schematic of an exemplary prior art stimulation pattern which can be used in the method of the present invention;
  • [0028]
    [0028]FIG. 5 is a schematic of an exemplary prior art pulse generator which can be used in the method of the present invention;
  • [0029]
    [0029]FIG. 6 is a sketch of an exemplary prior art catheter-type lead and electrode assembly which can be used in the method of the present invention;
  • [0030]
    [0030]FIG. 7 is a graph of known plasmal catecholamine levels in various physiologic and pathologic states;
  • [0031]
    [0031]FIGS. 8A, 8B, and 8C are exemplary graphs of the effect of splanchnic nerve stimulation on catecholamine release rates, epinephrine levels, and energy expenditure, respectively, which can be achieved in the practice of the present invention;
  • [0032]
    [0032]FIG. 9 is a graph of known plasma ghrelin levels over a daily cycle, for various subjects; and
  • [0033]
    [0033]FIG. 10 is a section view of an exemplary instrument placement which can be used in the method of the present invention, for implantation of an electrode assembly.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0034]
    The human nervous system is a complex network of nerve cells, or neurons, found centrally in the brain and spinal cord and peripherally in the various nerves of the body. Neurons have a cell body, dendrites and an axon. A nerve is a group of neurons that serve a particular part of the body. Nerves may contain several hundred neurons to several hundred thousand neurons. Nerves often contain both afferent and efferent neurons. Afferent neurons carry signals back to the central nervous system and efferent neurons carry signals to the periphery. A group of neuronal cell bodies in one location is known as a ganglion. Electrical signals are conducted via neurons and nerves. Neurons release neurotransmitters at synapses (connections) with other nerves to allow continuation and modulation of the electrical signal. In the periphery, synaptic transmission often occurs at ganglia.
  • [0035]
    The electrical signal of a neuron is known as an action potential. Action potentials are initiated when a voltage potential across the cell membrane exceeds a certain threshold. This action potential is then propagated down the length of the neuron. The action potential of a nerve is complex and represents the sum of action potentials of the individual neurons in it.
  • [0036]
    Neurons can be myelinated and unmyelinated, of large axonal diameter and small axonal diameter. In general, the speed of action potential conduction increases with myelination and with neuron axonal diameter. Accordingly, neurons are classified into type A, B and C neurons based on myelination, axon diameter, and axon conduction velocity. In terms of axon diameter and conduction velocity, A is greater than B which is greater than C.
  • [0037]
    The autonomic nervous system is a subsystem of the human nervous system that controls involuntary actions of the smooth muscles (blood vessels and digestive system), the heart, and glands, as shown in FIG. 1. The autonomic nervous system is divided into the sympathetic and parasympathetic systems. The sympathetic nervous system generally prepares the body for action by increasing heart rate, increasing blood pressure, and increasing metabolism. The parasympathetic system prepares the body for rest by lowering heart rate, lowering blood pressure, and stimulating digestion.
  • [0038]
    The hypothalamus controls the sympathetic nervous system via descending neurons in the ventral horn of the spinal cord, as shown in FIG. 2. These neurons synapse with preganglionic sympathetic neurons that exit the spinal cord and form the white communicating ramus. The preganglionic neuron will either synapse in the paraspinous ganglia chain or pass through these ganglia and synapse in a peripheral, or collateral, ganglion such as the celiac or mesenteric. After synapsing in a particular ganglion, a postsynaptic neuron continues on to innervate the organs of the body (heart, intestines, liver, pancreas, etc.) or to innervate the adipose tissue and glands of the periphery and skin. Preganglionic neurons of the sympathetic system are typically myelinated type B neurons and postganglionic neurons are typically unmyelinated type C neurons.
  • [0039]
    Several large sympathetic nerves and ganglia are formed by the neurons of the sympathetic nervous system as shown in FIG. 3. The greater splanchnic nerve (GSN) is formed by efferent sympathetic neurons exiting the spinal cord from thoracic vertebral segment numbers 4 or 5 (T4 or T5) through thoracic vertebral segment numbers 9 or 10 or 11 (T9, T10, or T11). The lesser splanchnic (lesser SN) nerve is formed by preganglionic fibers sympathetic efferent fibers from T10 to T12 and the least splanchnic nerve (least SN) is formed by fibers from T12. The GSN is typically present bilaterally in animals, including humans, with the other splanchnic nerves having a more variable pattern, present unilaterally or bilaterally and sometimes being absent. The splanchnic nerves run along the anterior-lateral aspect of the vertebral bodies and pass out of the thorax and enter the abdomen through the crus of the diaphragm. The nerves run in proximity to the azygous veins. Once in the abdomen, neurons of the GSN synapse with postganglionic neurons primarily in celiac ganglia. Some neurons of the GSN pass through the celiac ganglia and synapse on in the adrenal medulla. Neurons of the lesser SN and least SN synapse with post-ganglionic neurons in the mesenteric ganglia.
  • [0040]
    Postganglionic neurons, arising from the celiac ganglia that synapse with the GSN, innervate primarily the upper digestive system, including the stomach, pylorus, duodenum, pancreas, and liver. In addition, blood vessels and adipose tissue of the abdomen are innervated by neurons arising from the celiac ganglia/greater splanchnic nerve. Postganglionic neurons of the mesenteric ganglia, supplied by preganglionic neurons of the lesser and least splanchnic nerve, innervate primarily the lower intestine, colon, rectum, kidneys, bladder, and sexual organs, and the blood vessels that supply these organs and tissues.
  • [0041]
    In the treatment of obesity, the preferred embodiment involves electrical activation of the greater splanchnic nerve of the sympathetic nervous system. Preferably unilateral activation would be utilized, although bilateral activation could also be utilized. The celiac ganglia could also be activated, as well as the sympathetic chain or ventral spinal roots.
  • [0042]
    Electrical nerve modulation (nerve activation or inhibition) is accomplished by applying an energy signal (pulse) at a certain frequency to the neurons of a nerve (nerve stimulation). The energy pulse causes depolarization of neurons within the nerve above the activation threshold resulting in an action potential. The energy applied is a function of the current amplitude and pulse width duration. Activation or inhibition can be a function of the frequency, with low frequencies on the order of 1 to 50 Hz resulting in activation and high frequencies greater than 100 Hz resulting in inhibition. Inhibition can also be accomplished by continuous energy delivery resulting in sustained depolarization. Different neuronal types may respond to different frequencies and energies with activation or inhibition.
  • [0043]
    Each neuronal type (i.e., type A, B, or C neurons) has a characteristic pulse amplitude-duration profile (energy pulse signal) that leads to activation. Myelinated neurons (types A and B) can be stimulated with relatively low current amplitudes on the order of 0.1 to 5.0 milliamperes and short pulse widths on the order of 50 to 200 microseconds. Unmyelinated type C fibers typically require longer pulse widths on the order of 300 to 1,000 microseconds and higher current amplitudes. This difference in energy for activation can be utilized to selectively stimulate certain neurons in a nerve containing mixed neuronal types. This can be important in stimulating nerves such as the splanchnic, because the splanchnic nerves contains both afferent pain neurons, which are typically type C neurons, and efferent pre-ganglionic neurons, which are myelinated type B. If a therapy such as obesity treatment involves splanchnic nerve activation, it would be desirable to activate the efferent type B neurons and not the afferent type C pain neurons. This may be accomplished by varying the energy pulse signal.
  • [0044]
    Two important parameters related to stimulation of peripheral nerves of mixed neuronal type are the rheobase and chronaxie. These two parameters are a function of the stimulus duration and stimulus strength (current amplitude). The rheobase is the lower limit of the stimulus strength below which an action potential cannot be generated, regardless of the stimulus duration. The chronaxie is the stimulus duration corresponding to twice the rheobase. This is a measure of excitability of the mixed peripheral nerve. It is not desirable to stimulate a peripheral nerve at stimulus intensities greater than the chronaxie. The chronaxie of the splanchnic nerve is likely between approximately 150 microseconds and 400 microseconds.
  • [0045]
    Various stimulation patterns, ranging from continuous to intermittent, can be utilized. With intermittent stimulation, energy is delivered for a period of time at a certain frequency during the signal-on time as shown in FIG. 4. The signal-on time is followed by a period of time with no energy delivery, referred to as signal-off time.
  • [0046]
    Superimposed on the stimulation pattern are the treatment parameters, frequency and duration. The treatment frequency may be continuous or delivered at various time periods within the day or week. The treatment duration may last for as little as a few minutes to as long as several hours. For example, splanchnic nerve activation to treat obesity may be delivered at a frequency of three times daily, coinciding with meal times. Treatment duration with a specified stimulation pattern may last for one hour. Alternatively, treatment may be delivered at a higher frequency, say every three hours, for shorter durations, say 30 minutes. The treatment duration and frequency can be tailored to achieve the desired result.
  • [0047]
    Pulse generation for electrical nerve modulation is accomplished using a pulse generator. Pulse generators can use conventional microprocessors and other standard electrical components. A pulse generator for this embodiment can generate a pulse, or energy signal, at frequencies ranging from approximately 0.5 Hz to 300 Hz, a pulse width from approximately 10 to 1,000 microseconds, and a constant current of between approximately 0.1 milliamperes to 20 milliamperes. The pulse generator may be capable of producing a ramped, or sloped, rise in the current amplitude. The preferred pulse generator can communicate with an external programmer and or monitor. Passwords, handshakes and parity checks are employed for data integrity. The pulse generator can be battery operated or operated by an external radiofrequency device. Because the pulse generator, associated components, and battery may be implanted they are preferably encased in an epoxy-titanium shell.
  • [0048]
    A schematic of the implantable pulse generator (IPG) is shown in FIG. 5. Components are housed in the epoxy-titanium shell. The battery supplies power to the logic and control unit. A voltage regulator controls the battery output. The logic and control unit control the stimulus output and allow for programming of the various parameters such as pulse width, amplitude, and frequency. In addition, the stimulation pattern and treatment parameters can be programmed at the logic and control unit. A crystal oscillator provides timing signals for the pulse and for the logic and control unit. An antenna is used for receiving communications from an external programmer and for status checking the device. The output section couples to the electrodes and leads that carry the energy pulse to the nerve. The reed switch allows manual activation using an external magnet. Devices powered by an external radiofrequency device would limit the components to primarily a receiving coil or antenna.
  • [0049]
    The IPG is coupled to a lead and electrode assembly. The lead is a bundle of electrically conducting wires insulated from the surroundings by a non-electrically conducting coating. The wires of the lead connect the IPG to the stimulation electrodes, which transfers the energy pulse to the nerve. A single wire may connect the IPG to the electrode, or a wire bundle may connect the IPG to the electrode. Wire bundles may or may not be braided. Wire bundles are preferred because they increase reliability and durability. Alternatively, a helical wire assembly could be utilized to improve durability with flexion and extension of the lead.
  • [0050]
    The electrodes are preferably platinum or platinum-iridium ribbons or rings as shown in FIG. 6. The electrodes are capable of electrically coupling with the surrounding tissue and nerve. The electrodes may encircle a catheter-like lead assembly. The distal electrode may form a rounded cap at the end to create a bullet nose shape. Ideally, this electrode serves as the cathode. A lead of this type may contain 2 to 4 ring electrodes spaced anywhere from 2.0 to 5.0 mm apart with each ring electrode being approximately 1.0 to 10.0 mm in width. Catheter lead electrode assemblies may have an outer diameter of 0.5 mm to 1.5 mm to facilitate percutaneous placement using an introducer.
  • [0051]
    Bipolar stimulation of a nerve can be accomplished with multiple electrode assemblies with one electrode serving as the positive node and the other serving as a negative node. In this manner nerve activation can be directed primarily in one direction (unilateral), such as efferently, or away from the central nervous system. Alternatively, a nerve cuff electrode can be employed. Helical cuff electrodes as described in U.S. Pat. No. 5,251,634 to Weinberg are preferred. Cuff assemblies can similarly have multiple electrodes and direct and cause unilateral nerve activation.
  • [0052]
    Unipolar stimulation can also be performed. As used herein, unipolar stimulation means using only a single electrode on the lead, while the metallic shell of the IPG, or another external portion of the IPG, essentially functions as a second electrode, remote from the first electrode. This type of unipolar stimulation may be more suitable for splanchnic nerve stimulation than the bipolar stimulation method, particularly if the electrode is to be placed percutaneously under fluoroscopic visualization. With fluoroscopically observed percutaneous placement, it may not always be possible to place the electrodes immediately adjacent the nerve, which can be required for bipolar, stimulation. With unipolar stimulation, a larger energy field is created in order to electrically couple the electrode on the lead with the remote external portion of the IPG, and the generation of this larger energy field can result in activation of the nerve even in the absence of close proximity between the single lead electrode and the nerve. This allows successful nerve stimulation with the single electrode placed only in “general proximity” to the nerve, meaning that there can be significantly greater separation between the electrode and the nerve than the “close proximity” required for bipolar stimulation. The magnitude of the allowable separation between the electrode and the nerve will necessarily depend upon the actual magnitude of the energy field which the operator generates with the lead electrode in order to couple with the remote electrode.
  • [0053]
    In multiple electrode lead assemblies, some of the electrodes may be used for sensing nerve activity. This sensed nerve activity could serve as a signal to commence stimulation therapy. For example, afferent action potentials in the splanchnic nerve, created due to the commencement of feeding, could be sensed and used to activate the IPG to begin stimulation of the efferent neurons of the splanchnic nerve. Appropriate circuitry and logic for receiving and filtering the sensed signal would be required in the IPG.
  • [0054]
    Because branches of the splanchnic nerve directly innervate the adrenal medulla, electrical activation of the splanchnic nerve results in the release of catecholamines (epinephrine and norepinephrine) into the blood stream. In addition, dopamine and cortisol, which also raise energy expenditure, can be released. Catecholamines can increase energy expenditure by 15% to 20%. By comparison, subitramine, a pharmacologic agent used to treat obesity, increases energy expenditure by only 3% to 5%.
  • [0055]
    Human resting venous blood levels of norepinephrine and epinephrine are approximately 25 picograms (pg)/milliliter (ml) and 300 pg/ml, respectively, as shown in FIG. 7. Detectable physiologic changes such as increased heart rate occur at norepinephrine levels of approximately 1,500 pg/ml and epinephrine levels of approximately 50 pg/ml. Venous blood levels of norepinephrine can reach as high 2,000 pg/ml during heavy exercise, and levels of epinephrine can reach as high as 400 to 600 pg/ml during heavy exercise. Mild exercise produces norepinephrine and epinephrine levels of approximately 500 pg/ml and 100 pg/ml, respectively. It may be desirable to maintain catecholamine levels somewhere between mild and heavy exercise during electrical sympathetic activation treatment for obesity.
  • [0056]
    In anesthetized animals, electrical stimulation of the splanchnic nerve has shown to raise blood catecholamine levels in a frequency dependent manner in the range of 1 Hz to 20 Hz, such that rates of catecholamine release/production of 0.3 to 4.0 μg/min can be achieved. These rates are sufficient to raise plasma concentrations of epinephrine to as high as 400 to 600 pg/ml, which in turn can result in increased energy expenditure ranging from 10% to 20% as shown in FIG. 8. During stimulation, the ratio of epinephrine to norepinephrine is 65% to 35%. It may be possible to change the ratio by stimulating at higher frequencies. This may be desired to alter the energy expenditure and/or prevent a rise in MAP.
  • [0057]
    Energy expenditure in humans ranges from approximately 1.5 kcal/min to 2.5 kcal/min. A 15% increase in this energy expenditure in a person with a 2.0 kcal/min energy expenditure would increase expenditure by 0.3 kcal/min. Depending on treatment parameters, this could result in an additional 100 to 250 kcal of daily expenditure and 36,000 to 91,000 kcal of yearly expenditure. One pound of fat is approximately 3500 kcal, yielding an annual weight loss of 10 to 26 pounds.
  • [0058]
    Increased energy expenditure would need to be fueled by fat and carbohydrate metabolism. Postganglionic branches of the splanchnic nerve innervate the liver and fat deposits of the abdomen. Activation of the splanchnic nerve can result in fat metabolism and the liberation of fatty acids, as well as glycogen breakdown and the release of glucose from the liver. Fat metabolism coupled with increased energy expenditure may result in a net reduction in fat reserves.
  • [0059]
    It may also be desirable to titrate obesity therapy to plasma ghrelin levels. In humans, venous blood ghrelin levels range from approximately 250 pg/ml to greater than 700 pg/ml as shown in FIG. 9. Ghrelin levels rise and fall during the day with peak levels typically occurring just before meals. In patients with gastric bypass surgery, an effective treatment for obesity, ghrelin levels are more static and typically stay in a low range of 100 to 200 pg/ml. Splanchnic nerve activation, in the treatment of obesity, could be titrated to keep ghrelin levels in the low range below 250 to 300 pg/ml. Reductions in food intake comparable to the increases in energy expenditure (i.e. 100 to 250 kcal/day), could yield a total daily kcal reduction of 200 to 500 per day, and 20 to 50 pounds of weight loss per year.
  • [0060]
    In anesthetized animals, electrical activation of the splanchnic nerve has also been shown to decrease insulin secretion. In obesity, insulin levels are often elevated, and insulin resistant diabetes (Type II) is common. Down-regulation of insulin secretion by splanchnic nerve activation may help correct insulin resistant diabetes.
  • [0061]
    Electrical activation of the splanchnic nerve can cause an increase in mean arterial blood pressure (MAP) above a baseline value. A drop in MAP below the baseline can follow this increase. Because a sustained increase in MAP is undesirable, the stimulation pattern can be designed to prevent an increase in MAP. One strategy would be to have a relatively short signal-on time followed by a signal-off time of an equal or longer period. This would allow the MAP to drop back to or below the baseline. The subsequent signal-on time would then raise the MAP, but it may start from a lower baseline. In this manner a sinusoidal-like profile of the MAP could be set up during therapy delivery that would keep the average MAP within safe limits. The rise in MAP is accompanied by a decrease in heart rate which is a compensatory mechanism that may also normalize MAP with sustained stimulation for more than approximately 10 minutes.
  • [0062]
    Alternatively, an alpha-sympathetic receptor blocker, such a prazosin could be used to blunt the rise in MAP. Alpha-blockers are commonly available antihypertensive medications. The rise in MAP seen with splanchnic nerve stimulation is the result of alpha-receptor activation, which mediates arterial constriction. Because the affects of this therapy on reduced food intake and energy expenditure are related to beta-sympathetic receptor activity, addition of the alpha-blocker would not likely alter the therapeutic weight loss benefits.
  • [0063]
    Implantation of the lead/electrode assembly for activation of the greater splanchnic nerve is ideally accomplished percutaneously using an introducer as shown in FIG. 10. The introducer could be a hollow needle-like device that would be placed posteriorly through the skin between the ribs para-midline at the T9-T12 level of the thoracic spinal column. A posterior placement with the patient prone is preferred to allow bilateral electrode placement at the splanchnic nerves, if required. Placement of the needle could be guided using fluoroscopy, ultrasound, or CT scanning. Proximity to the splanchnic nerve by the introducer could be sensed by providing energy pulses to the introducer to electrically activate the nerve while monitoring for a rise in MAP. All but the very tip of the introducer would be electrically isolated so as to focus the energy delivered to the tip of the introducer. The lower the current amplitude required to cause a rise in the MAP, the closer the introducer tip would be to the nerve. Ideally, the introducer tip serves as the cathode for stimulation. Alternatively, a stimulation endoscope could be placed into the stomach of the patient for electrical stimulation of the stomach. The evoked potentials created in the stomach could be sensed in the splanchnic nerve by the introducer. To avoid damage to the spinal nerves, the introducer could sense evoked potentials created by electrically activating peripheral sensory nerves. Once the introducer was in proximity to the nerve, a catheter type lead electrode assembly would be inserted through the introducer and adjacent to the nerve. Stimulating the nerve and monitoring for a rise in MAP could be used to confirm electrode placement. The lead and the IPG would be implanted subcutaneously in the patient's back or side. The lead would be appropriately secured to avoid dislodgement. The lesser and least splanchnic nerves may also be activated to some degree by lead/electrode placement according to the above procedure, due to their proximity to the splanchnic nerve.
  • [0064]
    Percutaneous placement of the lead electrode assembly could be enhanced using direct or video assisted visualization. An optical port could be incorporated into the introducer. A separate channel would allow the electrode lead assembly to be inserted and positioned, once the nerve was visualized. Alternatively, a percutaneous endoscope could be inserted into the chest cavity for viewing advancement of the introducer to the nerve. The parietal lung pleuron is relatively clear, and the nerves and introducer can be seen running along the vertebral bodies. With the patient prone, the lungs are pulled forward by gravity creating a space for the endoscope and for viewing. This may avoid the need for single lung ventilation. If necessary, one lung could be collapsed to provide space for viewing. This is a common and safe procedure performed using a bifurcated endotracheal tube. The endoscope could also be placed laterally, and positive CO2 pressure could be used to push down the diaphragm, thereby creating a space for viewing and avoiding lung collapse.
  • [0065]
    Alternatively, stimulation electrodes could be placed along the sympathetic chain ganglia from approximately vertebra T4 to T11. This implantation could be accomplished in a similar percutaneous manner as above. This would create a more general activation of the sympathetic nervous system, though it would include activation of the neurons that comprise the splanchnic nerves.
  • [0066]
    Alternatively, the lead/electrode assembly could be placed intra-abdominally on the portion of the splanchnic nerve that resides retroperitoneally on the abdominal aorta just prior to synapsing in the celiac ganglia. Access to the nerve in this region could be accomplished laparoscopically, using typical laparoscopic techniques, or via open laparotomy. A cuff electrode could be used to encircle the nerve unilaterally or bilaterally. The lead could be anchored to the crus of the diaphragm. A cuff or patch electrode could also be attached to the celiac ganglia unilaterally or bilaterally. Similar activation of the splanchnic branches of the sympathetic nervous system would occur as implanting the lead electrode assembly in the thoracic region.
  • [0067]
    An alternative lead/electrode placement would be a transvascular approach. Due to the proximity of the splanchnic nerves to the azygous veins shown in FIG. 10, and in particular the right splanchnic nerve and right azygous vein, modulation could be accomplished by positioning a lead/electrode assembly in this vessel. Access to the venous system and azygous vein could occur via the subclavian vein using standard techniques. The electrode/lead assembly could be mounted on a catheter. A guidewire could be used to position the catheter in the azygous vein. The lead/electrode assembly would include an expandable member, such as a stent. The electrodes would be attached to the stent, and using balloon dilation of the expandable member, could be pressed against the vessel wall so that energy delivery could be transferred to the nerve. The expandable member would allow fixation of the electrode lead assembly in the vessel. The IPG and remaining lead outside of the vasculature would be implanted subcutaneously in a manner similar to a heart pacemaker.
  • [0068]
    While the particular invention as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages hereinbefore stated, it is to be understood that this disclosure is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended other than as described in the appended claims.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US14815 *6 May 1856 Manufacturing pelted yakns
US18367 *6 Oct 1857 William wilber
US3911930 *1 Mar 197414 Oct 1975Stimulation TechMethod and structure of preventing and treating ileus, and reducing acute pain by electrical pulse stimulation
US4573481 *25 Jun 19844 Mar 1986Huntington Institute Of Applied ResearchImplantable electrode array
US4595010 *12 Mar 198417 Jun 1986Bio-Research Associates, Inc.Electrical muscle stimulator
US4702254 *30 Dec 198527 Oct 1987Jacob ZabaraNeurocybernetic prosthesis
US4827935 *24 Apr 19869 May 1989Purdue Research FoundationDemand electroventilator
US4867164 *26 Oct 198719 Sep 1989Jacob ZabaraNeurocybernetic prosthesis
US5095905 *7 Jun 199017 Mar 1992Medtronic, Inc.Implantable neural electrode
US5107833 *2 Nov 199028 Apr 1992Medtronic, Inc.Telemetry gain adjustment algorithm and signal strength indication in a noisy environment
US5154172 *13 Nov 198913 Oct 1992Cyberonics, Inc.Constant current sources with programmable voltage source
US5179950 *5 Dec 199119 Jan 1993Cyberonics, Inc.Implanted apparatus having micro processor controlled current and voltage sources with reduced voltage levels when not providing stimulation
US5186170 *5 Dec 199116 Feb 1993Cyberonics, Inc.Simultaneous radio frequency and magnetic field microprocessor reset circuit
US5188104 *1 Feb 199123 Feb 1993Cyberonics, Inc.Treatment of eating disorders by nerve stimulation
US5205285 *14 Jun 199127 Apr 1993Cyberonics, Inc.Voice suppression of vagal stimulation
US5215086 *3 May 19911 Jun 1993Cyberonics, Inc.Therapeutic treatment of migraine symptoms by stimulation
US5215089 *21 Oct 19911 Jun 1993Cyberonics, Inc.Electrode assembly for nerve stimulation
US5222494 *31 Jul 199129 Jun 1993Cyberonics, Inc.Implantable tissue stimulator output stabilization system
US5231988 *9 Aug 19913 Aug 1993Cyberonics, Inc.Treatment of endocrine disorders by nerve stimulation
US5235980 *5 Dec 199117 Aug 1993Cyberonics, Inc.Implanted apparatus disabling switching regulator operation to allow radio frequency signal reception
US5237991 *19 Nov 199124 Aug 1993Cyberonics, Inc.Implantable medical device with dummy load for pre-implant testing in sterile package and facilitating electrical lead connection
US5251634 *3 May 199112 Oct 1993Cyberonics, Inc.Helical nerve electrode
US5263480 *7 Aug 199223 Nov 1993Cyberonics, Inc.Treatment of eating disorders by nerve stimulation
US5269303 *22 Feb 199114 Dec 1993Cyberonics, Inc.Treatment of dementia by nerve stimulation
US5299569 *3 May 19915 Apr 1994Cyberonics, Inc.Treatment of neuropsychiatric disorders by nerve stimulation
US5304206 *18 Nov 199119 Apr 1994Cyberonics, Inc.Activation techniques for implantable medical device
US5330515 *17 Jun 199219 Jul 1994Cyberonics, Inc.Treatment of pain by vagal afferent stimulation
US5335657 *3 May 19919 Aug 1994Cyberonics, Inc.Therapeutic treatment of sleep disorder by nerve stimulation
US5351394 *21 Sep 19924 Oct 1994Cyberonics, Inc.Method of making a nerve electrode array
US5423872 *26 May 199313 Jun 1995Cigaina; ValerioProcess and device for treating obesity and syndromes related to motor disorders of the stomach of a patient
US5454840 *5 Apr 19943 Oct 1995Krakovsky; Alexander A.Potency package
US5458626 *27 Dec 199317 Oct 1995Krause; Horst E.Method of electrical nerve stimulation for acceleration of tissue healing
US5531778 *20 Sep 19942 Jul 1996Cyberonics, Inc.Circumneural electrode assembly
US5540730 *6 Jun 199530 Jul 1996Cyberonics, Inc.Treatment of motility disorders by nerve stimulation
US5540734 *28 Sep 199430 Jul 1996Zabara; JacobCranial nerve stimulation treatments using neurocybernetic prosthesis
US5571150 *19 Dec 19945 Nov 1996Cyberonics, Inc.Treatment of patients in coma by nerve stimulation
US5690691 *8 May 199625 Nov 1997The Center For Innovative TechnologyGastro-intestinal pacemaker having phased multi-point stimulation
US5707400 *19 Sep 199513 Jan 1998Cyberonics, Inc.Treating refractory hypertension by nerve stimulation
US5716392 *5 Jan 199610 Feb 1998Medtronic, Inc.Minimally invasive medical electrical lead
US5725563 *20 Apr 199410 Mar 1998Klotz; AntoineElectronic device and method for adrenergically stimulating the sympathetic system with respect to the venous media
US5755750 *8 Nov 199626 May 1998University Of FloridaMethod and apparatus for selectively inhibiting activity in nerve fibers
US5782798 *26 Jun 199621 Jul 1998Medtronic, Inc.Techniques for treating eating disorders by brain stimulation and drug infusion
US5863994 *29 Sep 199726 Jan 1999Montell North America Inc.Using nitric oxide to reduce reactor fouling during polypropylene graft copolymerization
US5919216 *16 Jun 19976 Jul 1999Medtronic, Inc.System and method for enhancement of glucose production by stimulation of pancreatic beta cells
US5928272 *2 May 199827 Jul 1999Cyberonics, Inc.Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity
US5995872 *1 Oct 199830 Nov 1999Medtronic, Inc.Method and apparatus for electrical stimulation of the gastrointestinal tract
US6041258 *27 Jul 199821 Mar 2000Transneuronix, Inc.Medical stimulation
US6068596 *8 Oct 199730 May 2000Weth; GosbertMethod for administering a pulse-like wave to a patient for pain therapy and/or for influencing the autonomic nervous system
US6109269 *30 Apr 199929 Aug 2000Medtronic, Inc.Method of treating addiction by brain infusion
US6129685 *27 Jun 199710 Oct 2000The University Of Iowa Research FoundationStereotactic hypothalamic obesity probe
US6146391 *22 Jul 199914 Nov 2000Transneuronix, Inc.Laparoscopic forceps
US6165180 *13 Jan 200026 Dec 2000Transneuronix, Inc.Medical device handle for use in laparoscopic surgery
US6169924 *27 Apr 19992 Jan 2001T. Stuart MeloySpinal cord stimulation
US6308105 *15 Jul 199923 Oct 2001Medtronic Inc.Medical electrical stimulation system using an electrode assembly having opposing semi-circular arms
US6321124 *21 May 199820 Nov 2001Transneuronix, Inc.Implant device for electrostimulation and/or monitoring of endo-abdominal cavity tissue
US6350455 *2 Aug 200026 Feb 2002Allergan Sales, Inc.Method for treating a catecholamine secretion
US6356786 *20 Jan 200012 Mar 2002Electrocore Techniques, LlcMethod of treating palmar hyperhydrosis by electrical stimulation of the sympathetic nervous chain
US6356787 *24 Feb 200012 Mar 2002Electro Core Techniques, LlcMethod of treating facial blushing by electrical stimulation of the sympathetic nerve chain
US6381495 *10 Jan 200030 Apr 2002Transneuronix, Inc.Medical device for use in laparoscopic surgery
US6438423 *25 Jan 200020 Aug 2002Electrocore Technique, LlcMethod of treating complex regional pain syndromes by electrical stimulation of the sympathetic nerve chain
US6587719 *1 Jul 19991 Jul 2003Cyberonics, Inc.Treatment of obesity by bilateral vagus nerve stimulation
US6721603 *25 Jan 200213 Apr 2004Cyberonics, Inc.Nerve stimulation as a treatment for pain
US6885888 *23 Oct 200126 Apr 2005The Cleveland Clinic FoundationElectrical stimulation of the sympathetic nerve chain
US20010014815 *20 Dec 200016 Aug 2001Matsushita Electric Works, Ltd. And Toshihide YoshidaSlimming device
US20020072780 *25 Sep 200113 Jun 2002Transneuronix, Inc.Method and apparatus for intentional impairment of gastric motility and /or efficiency by triggered electrical stimulation of the gastrointestinal tract with respect to the intrinsic gastric electrical activity
US20020077675 *24 Sep 200120 Jun 2002Transneuronix, Inc.Minimally invasive surgery placement of stimulation leads in mediastinal structures
US20030018367 *19 Jul 200223 Jan 2003Dilorenzo Daniel JohnMethod and apparatus for neuromodulation and phsyiologic modulation for the treatment of metabolic and neuropsychiatric disease
US20030045909 *24 Jul 20026 Mar 2003Biocontrol Medical Ltd.Selective nerve fiber stimulation for treating heart conditions
US20030144708 *17 May 200231 Jul 2003Starkebaum Warren L.Methods and apparatus for retarding stomach emptying for treatment of eating disorders
US20040230255 *24 Feb 200418 Nov 2004Dobak John D.Splanchnic nerve stimulation for treatment of obesity
US20050149146 *31 Jan 20057 Jul 2005Boveja Birinder R.Method and system to provide therapy for obesity and other medical disorders, by providing electrical pules to symapthetic nerves or vagal nerve(s) with rechargeable implanted pulse generator
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US688588823 Oct 200126 Apr 2005The Cleveland Clinic FoundationElectrical stimulation of the sympathetic nerve chain
US70068715 Mar 200028 Feb 2006Metacure N.V.Blood glucose level control
US71677506 Jan 200423 Jan 2007Enteromedics, Inc.Obesity treatment with electrically induced vagal down regulation
US73370057 Sep 200526 Feb 2008Spinal Modulations, Inc.Methods for stimulating a nerve root ganglion
US73370067 Sep 200526 Feb 2008Spinal Modulation, Inc.Methods and systems for modulating neural tissue
US74441836 Jan 200428 Oct 2008Enteromedics, Inc.Intraluminal electrode apparatus and method
US74475467 Sep 20054 Nov 2008Spinal Modulation, Inc.Methods of neurostimulating targeted neural tissue
US74509937 Sep 200511 Nov 2008Spinal Modulation, Inc.Methods for selective stimulation of a ganglion
US748996929 Sep 200310 Feb 2009Enteromedics Inc.Vagal down-regulation obesity treatment
US75026517 Sep 200510 Mar 2009Spinal Modulation, Inc.Methods for stimulating a dorsal root ganglion
US752958221 Jun 20045 May 2009Dilorenzo Biomedical, LlcMethod and apparatus for neuromodulation and physiologic modulation for the treatment of metabolic and neuropsychiatric disease
US753293320 Oct 200412 May 2009Boston Scientific Scimed, Inc.Leadless cardiac stimulation systems
US753293812 Sep 200512 May 2009The Cleveland Clinic FoundationIntraluminal electrode assembly
US755196424 Feb 200423 Jun 2009Leptos Biomedical, Inc.Splanchnic nerve stimulation for treatment of obesity
US757099920 Dec 20054 Aug 2009Cardiac Pacemakers, Inc.Implantable device for treating epilepsy and cardiac rhythm disorders
US75807537 Sep 200525 Aug 2009Spinal Modulation, Inc.Method and system for stimulating a dorsal root ganglion
US758723811 Mar 20058 Sep 2009Cardiac Pacemakers, Inc.Combined neural stimulation and cardiac resynchronization therapy
US759973619 Jul 20026 Oct 2009Dilorenzo Biomedical, LlcMethod and apparatus for neuromodulation and physiologic modulation for the treatment of metabolic and neuropsychiatric disease
US762392430 Aug 200524 Nov 2009Leptos Biomedical, Inc.Devices and methods for gynecologic hormone modulation in mammals
US764388431 Jan 20055 Jan 2010Warsaw Orthopedic, Inc.Electrically insulated surgical needle assembly
US76471097 Mar 200512 Jan 2010Boston Scientific Scimed, Inc.Leadless cardiac stimulation systems
US76501867 Mar 200519 Jan 2010Boston Scientific Scimed, Inc.Leadless cardiac stimulation systems
US76645516 Jul 200516 Feb 2010Medtronic Transneuronix, Inc.Treatment of the autonomic nervous system
US767272717 Aug 20052 Mar 2010Enteromedics Inc.Neural electrode treatment
US768927618 Aug 200430 Mar 2010Leptos Biomedical, Inc.Dynamic nerve stimulation for treatment of disorders
US768927724 Jan 200630 Mar 2010Leptos Biomedical, Inc.Neural stimulation for treatment of metabolic syndrome and type 2 diabetes
US769357722 Jan 20076 Apr 2010Enteromedics Inc.Irritable bowel syndrome treatment
US770238624 Jan 200720 Apr 2010Leptos Biomedical, Inc.Nerve stimulation for treatment of obesity, metabolic syndrome, and Type 2 diabetes
US770501612 Feb 200427 Apr 2010Albert Einstein College Of Medicine Of Yeshiva UniversityRegulation of food intake by modulation of long-chain fatty acyl-CoA levels in the hypothalamus
US771143226 Jul 20054 May 2010Advanced Neuromodulation Systems, Inc.Stimulation system and method for treating a neurological disorder
US772054022 Jan 200718 May 2010Enteromedics, Inc.Pancreatitis treatment
US772519516 Feb 200725 May 2010Imthera Medical, Inc.RFID-based apparatus, system, and method for therapeutic treatment of obstructive sleep apnea
US772977113 Aug 20071 Jun 2010Enteromedics Inc.Nerve stimulation and blocking for treatment of gastrointestinal disorders
US773710929 Apr 200315 Jun 2010Temple University Of The Commonwealth System Of Higher EducationObesity controlling method
US782248617 Aug 200526 Oct 2010Enteromedics Inc.Custom sized neural electrodes
US784026210 Mar 200423 Nov 2010Impulse Dynamics NvApparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US784028121 Jul 200623 Nov 2010Boston Scientific Scimed, Inc.Delivery of cardiac stimulation devices
US784433830 Jun 200430 Nov 2010Enteromedics Inc.High frequency obesity treatment
US784882328 Aug 20067 Dec 2010Boston Scientific Scimed, Inc.Cardiac stimulation system
US786523712 Sep 20054 Jan 2011The Cleveland Clinic FoundationMethods and systems of achieving hemodynamic control through neuromodulation
US786524028 Dec 20074 Jan 2011Betastim, Ltd.Implantable pulse generator programming via electrodes
US786986727 Oct 200611 Jan 2011Cyberonics, Inc.Implantable neurostimulator with refractory stimulation
US786988426 Apr 200711 Jan 2011Cyberonics, Inc.Non-surgical device and methods for trans-esophageal vagus nerve stimulation
US786988528 Apr 200611 Jan 2011Cyberonics, IncThreshold optimization for tissue stimulation therapy
US78771464 May 200525 Jan 2011The Cleveland Clinic FoundationMethods of treating medical conditions by neuromodulation of the sympathetic nervous system
US790417526 Apr 20078 Mar 2011Cyberonics, Inc.Trans-esophageal vagus nerve stimulation
US792535113 Jun 200812 Apr 2011Betastim, Ltd.Gastrointestinal device for treating obesity and diabetes
US793714417 May 20073 May 2011Advanced Neuromodulation Systems, Inc.Electric modulation of sympathetic nervous system
US793714511 Jun 20073 May 2011Advanced Neuromodulation Systems, Inc.Dynamic nerve stimulation employing frequency modulation
US79371591 Apr 20103 May 2011Imthera Medical Inc.Apparatus, system and method for therapeutic treatment of obstructive sleep apnea
US793716131 Mar 20063 May 2011Boston Scientific Scimed, Inc.Cardiac stimulation electrodes, delivery devices, and implantation configurations
US796221427 Jul 200714 Jun 2011Cyberonics, Inc.Non-surgical device and methods for trans-esophageal vagus nerve stimulation
US797469623 Jul 20055 Jul 2011Dilorenzo Biomedical, LlcClosed-loop autonomic neuromodulation for optimal control of neurological and metabolic disease
US797470127 Apr 20075 Jul 2011Cyberonics, Inc.Dosing limitation for an implantable medical device
US798699522 Jan 200726 Jul 2011Enteromedics Inc.Bulimia treatment
US801020411 Mar 201030 Aug 2011Enteromedics Inc.Nerve blocking for treatment of gastrointestinal disorders
US802403517 May 200720 Sep 2011Advanced Neuromodulation Systems, Inc.Electric modulation of sympathetic nervous system
US804607517 Nov 200425 Oct 2011The Cleveland Clinic FoundationElectrical stimulation of the sympathetic nerve chain
US804608520 Oct 201025 Oct 2011Enteromedics Inc.Controlled vagal blockage therapy
US805077422 Dec 20051 Nov 2011Boston Scientific Scimed, Inc.Electrode apparatus, systems and methods
US807354310 Dec 20096 Dec 2011Stephen T. PylesMethod of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US80820397 Sep 200520 Dec 2011Spinal Modulation, Inc.Stimulation systems
US808813216 Dec 20053 Jan 2012Davol, Inc. (a C.R. Bard Company)Anastomotic outlet revision
US80924557 Feb 200510 Jan 2012Warsaw Orthopedic, Inc.Device and method for operating a tool relative to bone tissue and detecting neural elements
US809521813 Jul 200610 Jan 2012Betastim, Ltd.GI and pancreatic device for treating obesity and diabetes
US810334915 Dec 200924 Jan 2012Enteromedics Inc.Neural electrode treatment
US813136219 Aug 20096 Mar 2012Cardiac Pacemakers, Inc.Combined neural stimulation and cardiac resynchronization therapy
US814529912 Feb 201027 Mar 2012Advanced Neuromodulation Systems, Inc.Neural stimulation for treatment of metabolic syndrome and type 2 diabetes
US815050829 Mar 20073 Apr 2012Catholic Healthcare WestVagus nerve stimulation method
US815574411 Dec 200810 Apr 2012The Cleveland Clinic FoundationNeuromodulatory methods for treating pulmonary disorders
US817067428 Feb 20081 May 2012Advanced Neuromodulation Systems, Inc.Method of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US818521322 Oct 201022 May 2012Boston Scientific Scimed, Inc.Delivery of cardiac stimulation devices
US820460325 Apr 200819 Jun 2012Cyberonics, Inc.Blocking exogenous action potentials by an implantable medical device
US82046054 Feb 200919 Jun 2012Cardiac Pacemakers, Inc.Multi-site atrial electrostimulation
US8214047 *26 Sep 20053 Jul 2012Advanced Neuromodulation Systems, Inc.Method of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US821918829 Mar 200710 Jul 2012Catholic Healthcare WestSynchronization of vagus nerve stimulation with the cardiac cycle of a patient
US82244386 Jan 201017 Jul 2012Levin Bruce HMethod for directed intranasal administration of a composition
US82295642 Aug 201124 Jul 2012The Cleveland Clinic FoundationNeuromodulatory methods for treating pulmonary disorders
US822956511 Feb 200924 Jul 2012Spinal Modulation, Inc.Methods for stimulating a dorsal root ganglion
US823902824 Apr 20097 Aug 2012Cyberonics, Inc.Use of cardiac parameters in methods and systems for treating a chronic medical condition
US824437116 Mar 200614 Aug 2012Metacure LimitedPancreas lead
US826041631 Oct 20074 Sep 2012Impulse Dynamics, N.V.Electrical muscle controller
US828050510 Mar 20092 Oct 2012Catholic Healthcare WestVagus nerve stimulation method
US829060021 Jul 200616 Oct 2012Boston Scientific Scimed, Inc.Electrical stimulation of body tissue using interconnected electrode assemblies
US829592623 Oct 200923 Oct 2012Advanced Neuromodulation Systems, Inc.Dynamic nerve stimulation in combination with other eating disorder treatment modalities
US830124731 Oct 200730 Oct 2012Impulse Dynamics, N.V.Electrical muscle controller
US830661631 Oct 20076 Nov 2012Impulse Dynamics, N.V.Electrical muscle controller
US830661731 Oct 20076 Nov 2012Impulse Dynamics N.V.Electrical muscle controller
US831162918 Oct 200613 Nov 2012Impulse Dynamics, N.V.Electrical muscle controller
US832101331 Oct 200727 Nov 2012Impulse Dynamics, N.V.Electrical muscle controller and pacing with hemodynamic enhancement
US832103020 Apr 201027 Nov 2012Advanced Neuromodulation Systems, Inc.Esophageal activity modulated obesity therapy
US832641625 Oct 20104 Dec 2012Impulse Dynamics NvApparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US83320368 Mar 200711 Dec 2012Boston Scientific Scimed, Inc.Leadless cardiac stimulation systems
US83374041 Oct 201025 Dec 2012Flint Hills Scientific, LlcDetecting, quantifying, and/or classifying seizures using multimodal data
US834076012 Sep 201125 Dec 2012Advanced Neuromodulation Systems, Inc.Electric modulation of sympathetic nervous system
US834077119 Apr 201025 Dec 2012Advanced Neuromodulation Systems, Inc.Stimulation system and method treating a neurological disorder
US83407725 May 201025 Dec 2012Advanced Neuromodulation Systems, Inc.Brown adipose tissue utilization through neuromodulation
US83407807 May 200725 Dec 2012Scimed Life Systems, Inc.Leadless cardiac stimulation systems
US834636327 Dec 20051 Jan 2013Metacure LimitedBlood glucose level control
US835203124 May 20078 Jan 2013Impulse Dynamics NvProtein activity modification
US836428529 Dec 201029 Jan 2013The Cleveland Clinic FoundationElectrical stimulation of the sympathetic nerve chain
US83699527 Jul 20115 Feb 2013Enteromedics, Inc.Bulimia treatment
US838031824 Mar 201019 Feb 2013Spinal Modulation, Inc.Pain management with stimulation subthreshold to paresthesia
US838266729 Apr 201126 Feb 2013Flint Hills Scientific, LlcDetecting, quantifying, and/or classifying seizures using multimodal data
US838863220 Feb 20085 Mar 2013C.R. Bard, Inc.Tissue capturing and suturing device and method
US841233629 Dec 20092 Apr 2013Autonomic Technologies, Inc.Integrated delivery and visualization tool for a neuromodulation system
US84145597 May 20099 Apr 2013Rainbow Medical Ltd.Gastroretentive duodenal pill
US841734424 Oct 20089 Apr 2013Cyberonics, Inc.Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US842543010 Dec 200923 Apr 2013Warsaw Orthopedic, Inc.Electrically insulated surgical needle assembly
US84287252 Oct 200923 Apr 2013Imthera Medical, Inc.Method of stimulating a Hypoglossal nerve for controlling the position of a patient's tongue
US845238720 Sep 201028 May 2013Flint Hills Scientific, LlcDetecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US845774720 Oct 20084 Jun 2013Cyberonics, Inc.Neurostimulation with signal duration determined by a cardiac cycle
US846338518 Jun 201211 Jun 2013Stephen T. PylesMethod of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US84730621 May 200925 Jun 2013Autonomic Technologies, Inc.Method and device for the treatment of headache
US84784088 Mar 20072 Jul 2013Boston Scientific Scimed Inc.Leadless cardiac stimulation systems
US849464122 Apr 201023 Jul 2013Autonomic Technologies, Inc.Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism
US85180921 Jul 201127 Aug 2013Spinal Modulation, Inc.Hard tissue anchors and delivery devices
US853853319 Oct 201117 Sep 2013Enteromedics Inc.Controlled vagal blockage therapy
US853854221 Jul 201117 Sep 2013Enteromedics Inc.Nerve stimulation and blocking for treatment of gastrointestinal disorders
US85485834 May 20061 Oct 2013Impulse Dynamics NvProtein activity modification
US854859428 Feb 20121 Oct 2013Advanced Neuromodulation Systems, Inc.Stimulation system and method treating a neurological disorder
US855112013 Sep 20128 Oct 2013C.R. Bard, Inc.Tissue capturing and suturing device and method
US856253629 Apr 201022 Oct 2013Flint Hills Scientific, LlcAlgorithm for detecting a seizure from cardiac data
US856586725 Jan 200822 Oct 2013Cyberonics, Inc.Changeable electrode polarity stimulation by an implantable medical device
US857164316 Sep 201029 Oct 2013Flint Hills Scientific, LlcDetecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US858322929 Dec 201012 Nov 2013The Cleveland Clinic FoundationMethods of treating medical conditions by neuromodulation of the sympathetic nervous system
US861530929 Mar 200724 Dec 2013Catholic Healthcare WestMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US864164630 Jul 20104 Feb 2014Cyberonics, Inc.Seizure detection using coordinate data
US864493413 Sep 20074 Feb 2014Boston Scientific Scimed Inc.Cardiac stimulation using leadless electrode assemblies
US864987130 Apr 201011 Feb 2014Cyberonics, Inc.Validity test adaptive constraint modification for cardiac data used for detection of state changes
US86521403 Jan 201218 Feb 2014Warsaw Orthopedic, Inc.Device and method for operating a tool relative to bone tissue and detecting neural elements
US865544429 Oct 201218 Feb 2014Impulse Dynamics, N.V.Electrical muscle controller
US866066610 Mar 200925 Feb 2014Catholic Healthcare WestMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US866649518 Mar 20054 Mar 2014Metacure LimitedGastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US867900915 Jun 201025 Mar 2014Flint Hills Scientific, LlcSystems approach to comorbidity assessment
US868492115 May 20121 Apr 2014Flint Hills Scientific LlcDetecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
US87001614 Sep 200315 Apr 2014Metacure LimitedBlood glucose level control
US871254619 Mar 200829 Apr 2014Spinal Modulation, Inc.Neurostimulation system
US872523925 Apr 201113 May 2014Cyberonics, Inc.Identifying seizures using heart rate decrease
US873812610 Mar 200927 May 2014Catholic Healthcare WestSynchronization of vagus nerve stimulation with the cardiac cycle of a patient
US873814729 Jan 200927 May 2014Cardiac Pacemakers, Inc.Wireless tissue electrostimulation
US875100519 Mar 201310 Jun 2014Imthera Medical, Inc.Method of stimulating a hypoglossal nerve for controlling the position of a patients tongue
US87684713 Mar 20131 Jul 2014Cyberonics, Inc.Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US87815744 Mar 201315 Jul 2014Autonomic Technologies, Inc.Integrated delivery and visualization tool for a neuromodulation system
US879298520 Jan 200629 Jul 2014Metacure LimitedGastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US879298616 Feb 201029 Jul 2014Medtronic, Inc.Treatment of the autonomic nervous system
US880549430 Jul 201312 Aug 2014Cardiac Pacemakers, Inc.System and method to deliver therapy in presence of another therapy
US88251523 Apr 20022 Sep 2014Impulse Dynamics, N.V.Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue
US88251647 Jun 20112 Sep 2014Enteromedics Inc.Neural modulation devices and methods
US882791227 Apr 20109 Sep 2014Cyberonics, Inc.Methods and systems for detecting epileptic events using NNXX, optionally with nonlinear analysis parameters
US883173230 Apr 20109 Sep 2014Cyberonics, Inc.Method, apparatus and system for validating and quantifying cardiac beat data quality
US88382313 Jun 201116 Sep 2014Advanced Neuromodulation Systems, Inc.Neural Stimulation for treatment of metabolic syndrome and type 2 diabetes
US88494093 Mar 201330 Sep 2014Cyberonics, Inc.Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US885210025 Feb 20137 Oct 2014Flint Hills Scientific, LlcDetecting, quantifying, and/or classifying seizures using multimodal data
US885577024 Jul 20087 Oct 2014Betastim, Ltd.Duodenal eating sensor
US88622334 Feb 201314 Oct 2014Enteromedics Inc.Electrode band system and methods of using the system to treat obesity
US886821513 Jul 200921 Oct 2014Gep Technology, Inc.Apparatus and methods for minimally invasive obesity treatment
US88742162 Nov 200728 Oct 2014Gep Technology, Inc.Apparatus and methods for minimally invasive obesity treatment
US887421823 Apr 201328 Oct 2014Cyberonics, Inc.Neurostimulation with signal duration determined by a cardiac cycle
US888632228 Feb 201311 Nov 2014Imthera Medical, Inc.System for stimulating a hypoglossal nerve for controlling the position of a patient's tongue
US888632510 Jul 201311 Nov 2014Autonomic Technologies, Inc.Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism
US88887023 Dec 201218 Nov 2014Flint Hills Scientific, LlcDetecting, quantifying, and/or classifying seizures using multimodal data
US89349751 Feb 201113 Jan 2015Metacure LimitedGastrointestinal electrical therapy
US894500624 Feb 20143 Feb 2015Flunt Hills Scientific, LLCDetecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
US894885521 May 20133 Feb 2015Flint Hills Scientific, LlcDetecting and validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US895887217 Feb 201417 Feb 2015Impulse Dynamics, N.V.Electrical muscle controller
US897735320 Aug 201310 Mar 2015Impulse Dynamics NvProtein activity modification
US898360930 May 200817 Mar 2015The Cleveland Clinic FoundationApparatus and method for treating pulmonary conditions
US89836246 Dec 200717 Mar 2015Spinal Modulation, Inc.Delivery devices, systems and methods for stimulating nerve tissue on multiple spinal levels
US898986216 Aug 201124 Mar 2015The Cleveland Clinic FoundationApparatus and method for treating pulmonary conditions
US902058230 Sep 201328 Apr 2015Flint Hills Scientific, LlcDetecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US903165424 Apr 201412 May 2015Imthera Medical, Inc.Method of stimulating a hypoglossal nerve for controlling the position of a patient's tongue
US904459229 Jan 20082 Jun 2015Spinal Modulation, Inc.Sutureless lead retention features
US905046924 Nov 20049 Jun 2015Flint Hills Scientific, LlcMethod and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals
US905619727 Oct 200916 Jun 2015Spinal Modulation, Inc.Selective stimulation systems and signal parameters for medical conditions
US907291127 Jun 20137 Jul 2015Boston Scientific Scimed, Inc.Leadless cardiac stimulation systems
US910176516 Feb 200611 Aug 2015Metacure LimitedNon-immediate effects of therapy
US910804125 Nov 201318 Aug 2015Dignity HealthMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US910805712 Oct 201018 Aug 2015The Cleveland Clinic FoundationMethods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system
US916206216 Sep 201320 Oct 2015Enteromedics Inc.Controlled vagal blockage therapy
US91740405 Sep 20133 Nov 2015Enteromedics Inc.Nerve stimulation and blocking for treatment of gastrointestinal disorders
US918651413 Feb 201517 Nov 2015Impulse Dynamics NvElectrical muscle controller
US920525922 Feb 20128 Dec 2015The Board Of Trustees Of The Leland Stanford Junior UniversityNeurostimulation system
US920526016 Jul 20128 Dec 2015The Board Of Trustees Of The Leland Stanford Junior UniversityMethods for stimulating a dorsal root ganglion
US92052615 Dec 20128 Dec 2015The Board Of Trustees Of The Leland Stanford Junior UniversityNeurostimulation methods and systems
US92209107 Jan 201429 Dec 2015Cyberonics, Inc.Seizure detection using coordinate data
US924164721 Oct 201326 Jan 2016Cyberonics, Inc.Algorithm for detecting a seizure from cardiac data
US925956914 May 201016 Feb 2016Daniel M. BrounsteinMethods, systems and devices for neuromodulating spinal anatomy
US92895993 Apr 201222 Mar 2016Dignity HealthVagus nerve stimulation method
US928961823 Oct 200122 Mar 2016Impulse Dynamics NvElectrical muscle controller
US930837421 May 201212 Apr 2016Boston Scientific Scimed, Inc.Delivery of cardiac stimulation devices
US93146186 Dec 200719 Apr 2016Spinal Modulation, Inc.Implantable flexible circuit leads and methods of use
US931463331 Aug 201219 Apr 2016Cyberonics, Inc.Contingent cardio-protection for epilepsy patients
US93146419 Apr 201519 Apr 2016Imthera Medical, Inc.Method of stimulating a hypoglossal nerve for controlling the position of a patient's tongue
US932090815 Jan 201026 Apr 2016Autonomic Technologies, Inc.Approval per use implanted neurostimulator
US93271102 Feb 20123 May 2016St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”)Devices, systems and methods for the targeted treatment of movement disorders
US93396517 Oct 201417 May 2016Imthera Medical, Inc.System for stimulating a hypoglossal nerve for controlling the position of a patient's tongue
US93583956 Aug 20147 Jun 2016Enteromedics Inc.Neural modulation devices and methods
US93813496 Jun 20145 Jul 2016Bhl Patent Holdings LlcApparatus for treating cerebral neurovascular disorders including headaches by neural stimulation
US939340529 Apr 201419 Jul 2016Cardiac Pacemakers, Inc.Wireless tissue electrostimulation
US940255029 Apr 20112 Aug 2016Cybertronics, Inc.Dynamic heart rate threshold for neurological event detection
US940902129 May 20159 Aug 2016St. Jude Medical Luxembourg Holdings SMI S.A.R.L.Selective stimulation systems and signal parameters for medical conditions
US94275706 Dec 200730 Aug 2016St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”)Expandable stimulation leads and methods of use
US94400809 Mar 201513 Sep 2016Impulse Dynamics NvProtein activity modification
US94687625 Feb 201518 Oct 2016St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”)Pain management with stimulation subthreshold to paresthesia
US948663330 Nov 20158 Nov 2016The Board Of Trustees Of The Leland Stanford Junior UniversitySelective stimulation to modulate the sympathetic nervous system
US949816225 Apr 201122 Nov 2016Cyberonics, Inc.Identifying seizures using heart data from two or more windows
US950439013 Sep 201329 Nov 2016Globalfoundries Inc.Detecting, assessing and managing a risk of death in epilepsy
US95048368 Jul 201429 Nov 2016Cardiac Pacemakers, Inc.System and method to deliver therapy in presence of another therapy
US953315110 Jan 20143 Jan 2017Dignity HealthMicroburst electrical stimulation of cranial nerves for the treatment of medical conditions
US954551324 Mar 201417 Jan 2017Cardiac Pacemakers, Inc.Leadless cardiac stimulation systems
US955469423 Jun 201431 Jan 2017Autonomic Technologies, Inc.Integrated delivery and visualization tool for a neuromodulation system
US95795057 Mar 201628 Feb 2017Imthera Medical, Inc.Method of stimulating a hypoglossal nerve for controlling the position of a patient's tongue
US95860468 Sep 20147 Mar 2017Enteromedics, Inc.Electrode band system and methods of using the system to treat obesity
US958604721 Nov 20157 Mar 2017Cyberonics, Inc.Contingent cardio-protection for epilepsy patients
US962323326 Feb 201518 Apr 2017St. Jude Medical Luxembourg Holdings SMI S.A.R.L. (“SJM LUX SMI”)Delivery devices, systems and methods for stimulating nerve tissue on multiple spinal levels
US9662486 *30 Apr 201530 May 2017Ethicon Endo-Surgery, Inc.Methods and devices for activating brown adipose tissue using electrical energy
US96624872 Mar 201630 May 2017Boston Scientific Scimed, Inc.Delivery of cardiac stimulation devices
US96624976 Apr 201630 May 2017Imthera Medical, IncSystem for stimulating a hypoglossal nerve for controlling the position of a patient's tongue
US968188023 Oct 201320 Jun 2017Warsaw Orthopedic, Inc.Device and method for operating a tool relative to bone tissue and detecting neural elements
US96822332 Nov 201520 Jun 2017Enteromedics Inc.Nerve stimulation and blocking for treatment of gastrointestinal disorders
US97002567 Dec 201511 Jul 2017Cyberonics, Inc.Algorithm for detecting a seizure from cardiac data
US971372312 Feb 200725 Jul 2017Impulse Dynamics NvSignal delivery through the right ventricular septum
US20020116030 *23 Oct 200122 Aug 2002Rezai Ali R.Electrical stimulation of the sympathetic nerve chain
US20030018367 *19 Jul 200223 Jan 2003Dilorenzo Daniel JohnMethod and apparatus for neuromodulation and phsyiologic modulation for the treatment of metabolic and neuropsychiatric disease
US20040172086 *29 Sep 20032 Sep 2004Beta Medical, Inc.Nerve conduction block treatment
US20040172088 *6 Jan 20042 Sep 2004Enteromedics, Inc.Intraluminal electrode apparatus and method
US20040176812 *29 Sep 20039 Sep 2004Beta Medical, Inc.Enteric rhythm management
US20040230255 *24 Feb 200418 Nov 2004Dobak John D.Splanchnic nerve stimulation for treatment of obesity
US20050065573 *17 Nov 200424 Mar 2005Rezai Ali R.Electrical stimulation of the sympathetic nerve chain
US20050065575 *18 Aug 200424 Mar 2005Dobak John D.Dynamic nerve stimulation for treatment of disorders
US20050070974 *12 Jan 200431 Mar 2005Knudson Mark B.Obesity and eating disorder stimulation treatment with neural block
US20050149146 *31 Jan 20057 Jul 2005Boveja Birinder R.Method and system to provide therapy for obesity and other medical disorders, by providing electrical pules to symapthetic nerves or vagal nerve(s) with rechargeable implanted pulse generator
US20050245986 *30 Apr 20043 Nov 2005Medtronic, Inc.Heart rate variability control of gastric electrical stimulator
US20060020298 *23 Aug 200426 Jan 2006Camilleri Michael LSystems and methods for curbing appetite
US20060047325 *26 Jul 20052 Mar 2006Mark ThimineurStimulation system and method for treating a neurological disorder
US20060052826 *7 Sep 20059 Mar 2006Kim Daniel HPulse generator for high impedance electrodes
US20060052827 *7 Sep 20059 Mar 2006Kim Daniel HStimulation systems
US20060052828 *7 Sep 20059 Mar 2006Kim Daniel HMethods for stimulating a nerve root ganglion
US20060052835 *7 Sep 20059 Mar 2006Kim Daniel HMethods for stimulating the spinal cord and nervous system
US20060052836 *7 Sep 20059 Mar 2006Kim Daniel HNeurostimulation system
US20060052837 *7 Sep 20059 Mar 2006Kim Daniel HMethods and systems for modulating neural tissue
US20060052838 *7 Sep 20059 Mar 2006Kim Daniel HMethods of neurostimulating targeted neural tissue
US20060052839 *7 Sep 20059 Mar 2006Kim Daniel HMethods for stimulating a dorsal root ganglion
US20060052856 *7 Sep 20059 Mar 2006Kim Daniel HStimulation components
US20060058597 *12 Sep 200516 Mar 2006Andre MachadoIntraluminal electrode assembly
US20060058851 *6 Jul 200516 Mar 2006Valerio CigainaTreatment of the autonomic nervous system
US20060074456 *26 Sep 20056 Apr 2006Advanced Neuromodulation Systems, Inc.Method of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US20060079943 *30 Aug 200513 Apr 2006Narciso Hugh L JrDevices and methods for gynecologic hormone modulation in mammals
US20060085039 *20 Oct 200420 Apr 2006Hastings Roger NLeadless cardiac stimulation systems
US20060085046 *12 Sep 200520 Apr 2006Ali RezaiMethods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system
US20060116736 *22 Dec 20051 Jun 2006Dilorenzo Daniel JMethod, apparatus, and surgical technique for autonomic neuromodulation for the treatment of obesity
US20060167498 *13 Jun 200527 Jul 2006Dilorenzo Daniel JMethod, apparatus, and surgical technique for autonomic neuromodulation for the treatment of disease
US20060173374 *31 Jan 20053 Aug 2006Neubardt Seth LElectrically insulated surgical probing tool
US20060173521 *31 Jan 20053 Aug 2006Pond John D JrElectrically insulated surgical needle assembly
US20060178593 *7 Feb 200510 Aug 2006Neubardt Seth LDevice and method for operating a tool relative to bone tissue and detecting neural elements
US20060178594 *7 Feb 200510 Aug 2006Neubardt Seth LApparatus and method for locating defects in bone tissue
US20060190053 *24 Jan 200624 Aug 2006Dobak John D IiiNeural stimulation for treatment of metabolic syndrome and type 2 diabetes
US20060206154 *11 Mar 200514 Sep 2006Julia MoffittCombined neural stimulation and cardiac resynchronization therapy
US20070016262 *11 Apr 200618 Jan 2007Betastim, Ltd.Gi and pancreatic device for treating obesity and diabetes
US20070043400 *17 Aug 200522 Feb 2007Donders Adrianus PNeural electrode treatment
US20070060954 *27 Feb 200615 Mar 2007Tracy CameronMethod of using spinal cord stimulation to treat neurological disorders or conditions
US20070162085 *9 Mar 200712 Jul 2007Dilorenzo Biomedical, LlcMethod, apparatus, surgical technique, and stimulation parameters for autonomic neuromodulation for the treatment of obesity
US20070203521 *24 Jan 200730 Aug 2007Leptos Biomedical, Inc.Nerve stimulation for treatment of obesity, metabolic syndrome, and type 2 diabetes
US20070203531 *30 Apr 200430 Aug 2007Medtronic, Inc.Heart rate variability control of gastric electrical stimulator
US20070219596 *17 May 200720 Sep 2007Leptos Biomedical, Inc.Electric modulation of sympathetic nervous sytem
US20070233204 *16 Feb 20074 Oct 2007Lima Marcelo GRFID-based apparatus, system, and method for therapeutic treatment of a patient
US20080004671 *26 Jun 20073 Jan 2008Alza CorporationVagus nerve stimulation via orally delivered apparatus
US20080033511 *11 Jun 20077 Feb 2008Leptos Biomedical, Inc.Dynamic nerve stimulation employing frequency modulation
US20080046012 *7 Sep 200721 Feb 2008Alejandro CovalinMethod and system for modulating energy expenditure and neurotrophic factors
US20080109046 *16 Feb 20078 May 2008Lima Marcelo GRFID-based apparatus, system, and method for therapeutic treatment of obstructive sleep apnea
US20080154329 *28 Feb 200826 Jun 2008Advanced Neuromodulation Systems, Inc.Method of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US20080161787 *16 Dec 20053 Jul 2008Mitchell RoslinAnastomotic Outlet Revision
US20080183237 *16 Apr 200731 Jul 2008Electrocore, Inc.Methods And Apparatus For Treating Ileus Condition Using Electrical Signals
US20080208305 *17 Jan 200828 Aug 2008The Cleveland Clinic FoundationApparatus and methods for treating pulmonary conditions
US20080281365 *9 May 200713 Nov 2008Tweden Katherine SNeural signal duty cycle
US20090030473 *13 Jun 200829 Jan 2009Betastim, Ltd.Gastrointestinal device for treating obesity and diabetes
US20090062881 *13 Jul 20065 Mar 2009Betastim, Ltd.Gi and pancreatic device for treating obesity and diabetes
US20090118777 *2 Aug 20087 May 2009Kobi IkiEfferent and afferent splanchnic nerve stimulation
US20090155336 *11 Dec 200818 Jun 2009The Cleveland Clinic FoundationNeuromodulatory methods for treating pulmonary disorders
US20090171410 *28 Dec 20072 Jul 2009Betastim, Ltd.Implantable pulse generator programming via electrodes
US20090259279 *22 Jun 200915 Oct 2009Dobak Iii John DSplanchnic nerve stimulation for treatment of obesity
US20090270943 *25 Apr 200829 Oct 2009Maschino Steven EBlocking Exogenous Action Potentials by an Implantable Medical Device
US20090299439 *2 Jun 20083 Dec 2009Warsaw Orthopedic, Inc.Method, system and tool for surgical procedures
US20100057178 *11 Sep 20094 Mar 2010Electrocore, Inc.Methods and apparatus for spinal cord stimulation using expandable electrode
US20100094379 *2 Oct 200915 Apr 2010Imthera Medical, Inc.Method of Stimulating a Hypoglossal Nerve for Controlling the Position of a Patient's Tongue
US20100106207 *23 Oct 200929 Apr 2010Leptos Biomedical, Inc.Dynamic nerve stimulation in combination with other eating disorder treatment modalities
US20100145408 *12 Feb 201010 Jun 2010Dobak Iii John DSplanchnic Nerve Stimulation For Treatment of Obesity
US20100145428 *22 Feb 201010 Jun 2010Advanced Neuromodulation Systems, Inc.Method of using spinal cord stimulation to treat neurological disorders or conditions
US20100174339 *10 Dec 20098 Jul 2010Pyles Stephen TMethod of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions
US20100204749 *19 Apr 201012 Aug 2010Advanced Neuromodulation Systems, Inc.Stimulation system and method treating a neurological disorder
US20100234907 *12 Feb 201016 Sep 2010Dobak Iii John DSplanchnic Nerve Stimulation for Treatment of Obesity
US20100249889 *12 Feb 201030 Sep 2010Dobak Iii John DNeural Stimulation For Treatment of Metabolic Syndrome and Type 2 Diabetes
US20100298741 *24 Jul 200825 Nov 2010Betastim, Ltd.Duodenal eating sensor
US20100305664 *1 Jun 20102 Dec 2010Wingeier Brett MMethods and Devices for Adrenal Stimulation
US20110029037 *12 Oct 20103 Feb 2011The Cleveland Clinic FoundationMethods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system
US20110098762 *29 Dec 201028 Apr 2011The Cleveland Clinic FoundationElectrical stimulation of the sympathetic nerve chain
US20110098778 *19 Apr 201028 Apr 2011Advanced Neuromodulation Systems, Inc.Stimulation system and method treating a neurological disorder
US20130131636 *8 Jan 201323 May 2013The Cleveland Clinic FoundationMethods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system
US20130178829 *1 Mar 201311 Jul 2013Autonomic Technologies, Inc.Methods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system
US20140052214 *28 Oct 201320 Feb 2014The Cleveland Clinic FoundationElectrical stimulation of the sympathetic nerve chain
US20140316268 *6 Feb 201423 Oct 2014Ronny KafiluddiPeripheral nerve identification
US20150119867 *7 Mar 201330 Apr 2015Medtronic Ardian Luxembourg SarlGastrointestinal neuromodulation and associated systems and methods
US20150258326 *30 Apr 201517 Sep 2015Ethicon-Endo Surgery, Inc.Methods and Devices for Activating Brown Adipose Tissue Using Electrical Energy
EP1778341A1 *16 Aug 20052 May 2007Leptos Biomedical, Inc.Dynamic nerve stimulation for treatment of disorders
EP1778341A4 *16 Aug 20052 Feb 2011Advanced Neuromodulation SysDynamic nerve stimulation for treatment of disorders
EP1793893A2 *7 Sep 200513 Jun 2007Spinal Modulation Inc.Neurostimulation methods and systems
EP1793893A4 *7 Sep 200518 Mar 2009Spinal Modulation IncNeurostimulation methods and systems
EP1863561A2 *15 Mar 200612 Dec 2007The Regents Of The University Of CaliforniaMethod and system for modulating energy expenditure and neurotrophic factors
EP1863561A4 *15 Mar 200620 Apr 2011Univ CaliforniaMethod and system for modulating energy expenditure and neurotrophic factors
EP2010272A2 *17 Apr 20077 Jan 2009Electrocore, Inc.Methods and apparatus for treating ileus condition using electrical signals
EP2010272A4 *17 Apr 200724 Nov 2010Electrocore IncMethods and apparatus for treating ileus condition using electrical signals
WO2006014896A1 *26 Jul 20059 Feb 2006Advanced Neuromodulation Systems, Inc.Stimulation system and method treating a neurological disorder
WO2006026704A2 *31 Aug 20059 Mar 2006Leptos Biomedical, Inc.Devices and methods for gynecologic hormone modulation in mammals
WO2006026704A3 *31 Aug 200510 May 2007Leptos Biomedical IncDevices and methods for gynecologic hormone modulation in mammals
WO2006029257A27 Sep 200516 Mar 2006Spinal Modulation Inc.Neurostimulation methods and systems
WO2006083883A1 *31 Jan 200610 Aug 2006Warsaw Orthopedic, Inc.Electrically insulated surgical probing tool
WO2007007339A3 *13 Jul 200630 Apr 2009Betastim LtdGi and pancreatic device for treating obesity and diabetes
WO2016141184A1 *3 Mar 20169 Sep 2016Georgia Tech Research CorporationGlucose regulation via electrical stimulation of nerves innervating the liver
Classifications
U.S. Classification607/58
International ClassificationA61N1/05, A61N1/32, A61N1/34
Cooperative ClassificationA61N1/36007, A61N1/36071, A61N1/36085, A61N1/36017
European ClassificationA61N1/36Z, A61N1/36Z3C, A61N1/36E, A61N1/36E4, A61N1/36
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